Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma. The disease remains a major neglected, poverty-related health problem in many tropical areas. It is estimated that more than 200 million people are infected with schistosomiasis, resulting in 280,000 deaths annually while more than 20 million infected individuals experience high morbidity.
Currently chemotherapy is the main schistosomiasis control method and is mediated largely through the use of praziquantel (PZQ). The low cost of the drug and its efficacy against adult worms of all schistosome species that infect humans has lead to its very widespread use; currently tens of millions receive annual treatments of PZQ. However, because of high reinfection rates, PZQ must be administered on an annual or semi-annual basis.
There is a danger that widespread reliance on a single drug for schistosomiasis control will hasten the selection of drug-resistant parasites. In fact, twelve PZQ resistant isolates of Schistosoma mansoni have been obtained from schistosomiasis patients in Egypt. Four of the PZQ chemotherapy resistant parasites were accredited to host factors while eight of these isolates were implicated to be worm factors. There are also reports of S. haematobium patients who continued to pass eggs after at least two PZQ treatments. Moreover, PZQ resistant parasites have been selected for in the laboratory.
Artemether has shown promise as a new drug for schistosomiasis, although its use for schistosomiasis may be restricted in areas of malaria transmission so that its use as an antimalarial is not put at risk. Oxamniquine, a single dose anthelmintic drug is effective only against S. mansoni and resistance to oxamniquine has been reported further reducing its potential value in schistosomiasis control. The dependence on a single drug for the treatment of schistosomiasis is not sustainable; there is an urgent need for new drugs and drug targets for schistosomiasis treatment.
Schistosome parasites have a complex lifecycle involving snail intermediate and human definitive hosts. Humans become infected when contacting water containing cercariae released by infected snails. After penetration, cercariae remain in the skin for several days, then enter the general circulation and are carried to the lungs, where they reside for several further days before finally entering the liver. Once in the liver, parasites undergo rapid growth, development and sexual differentiation and locate a mate. After pairing, adult parasites migrate to the mesenteric venules (S. mansoni and S. japonicum) or the venules of the urogenital system (S. haematobium) of their human host where they commence egg production.